49. Liver Amylase and Hyperglycaemia

THE breakdown of liver glycogen which occurs as one of the chief mechanisms controlling the blood sugar level has generally been ascribed to the liver amylase, but it has recently been suggested that the main path of glycogen breakdown may be through a phosphorylating system involving a phosphorylase which forms hexosephosphate and a phosphatase which hydrolyses the hexosephosphate to glucose [Cori & Cori, 1938]. Recent work has added greatly to our knowledge of the phosphorylating mechanism in the liver [Cori et at. 1939; Ostern et al. 1939], but if the glycogen breakdown in vivo is to be ascribed to this system it would leave the significance of the liver amylase in doubt and there is as yet little reason for attributing this function to the one system rather than to the other. Cori & Cori [1938] have suggested that the amylase found in the liver may be due to the blood contained in the organ and quote in this connexion an older observation of Davenport [1926] that little amylase is found in the liver after thorough perfusion: but other investigators have concluded that perfusion washes the amylase out of the tissues [Lesser, 1920; WillstiLtter & Rohdewald, 1936]. There is therefore some doubt as to whether the amylase is really present in the liver tissues or not. The question of the exact localization of the amylase is of special interest since Lesser [1921] concluded that the glycogen and amylase are spatially separated in the liver and that adrenaline acts in producing hyperglycaemia by enabling the glycogen and amylase to come together. The phosphorylating system has been shown to be reversible, catalysing either the breakdown or the synthesis of glycogen. It is unlikely that there would be more than one system that is able to synthesize glycogen and it is therefore probable that this system is concerned in the synthesis of glycogen in vivo; but it is not known that the path of glycogen breakdown in vivo is the same as that by which it is synthesized. It is also not known that the mechanism concerned in the normal regulation of the blood sugar is the same as that which comes into action in causing the rapid glycogen breakdown which occurs in the various forms of endogenous hyperglycaemia. In considering the possible significance of the liver amylase and phosphorylase in relation to hyperglycaemia it is clear that much further information is required before it is possible to reach any final conclusions. In the present investigation particular attention was paid to the significance of the liver amylase and an attempt was made to obtain further evidence on the following questions. (1) Is the amylase present in significant amount in the liver tissue? (2) How are the amylase and phosphorylase distributed between the cells, lymph and blood spaces in the liver? (3) How does the activity of the liver amylase compare with the rate of glycogenolysis which occurs during hyperglycaemia in vivo?